Source:http://linkedlifedata.com/resource/pubmed/id/20624462
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions |
umls-concept:C0024399,
umls-concept:C0025260,
umls-concept:C0035015,
umls-concept:C0035647,
umls-concept:C0035820,
umls-concept:C0039194,
umls-concept:C0085358,
umls-concept:C0205263,
umls-concept:C0205430,
umls-concept:C0333678,
umls-concept:C0376152,
umls-concept:C1167395,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1548437,
umls-concept:C1706438,
umls-concept:C1882923,
umls-concept:C2698600
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| pubmed:issue |
4
|
| pubmed:dateCreated |
2010-8-30
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| pubmed:abstractText |
Mixed hematopoietic chimerism provides a powerful means of achieving transplantation tolerance. We investigated the efficacy of combined blockade of the CD40/CD154 and CD28/B7 costimulation pathways to induce sustained mixed chimerism in cynomolgus monkeys following major histocompatibility complex-mismatched bone marrow (BM) transplants. A nonmyeloablative conditioning regimen of busulfan, intravenous and intraosseous ifosfamide, and anti-thymocyte globulin was used. BM transplantation was followed by a one-week course of CTLA4-Ig/anti-CD154 monoclonal antibodies. Three recipients achieved a wide range of transient chimerism (10.8-79.8%). A rapid proliferation of host effector memory (CD28(low)CD95(high)) CD8(+) T cells was observed in conditioned animals whether or not they received allogeneic BM, and this expansion occurred concurrently with the loss of chimerism in BM recipients. CD8(+) T cells from the recipients had increased reactivity to donor stimulators vs. third-party stimulators. Additional immunosuppression with tacrolimus or deoxyspergualin after transplantation delayed post-transplant proliferation of effector memory CD8(+) T cells but did not promote chimerism. A one-month course of costimulatory blockade also did not prevent marrow rejection. These studies demonstrate that combined CD40/CD154 and CD28/B7 costimulatory blockade supports transient mixed chimerism induction following nonmyeloablative conditioning in primates, but is insufficient to overcome host immune resistance likely mediated by effector memory CD8(+) T cells.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
1878-5492
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| pubmed:author |
pubmed-author:AbeRyoR,
pubmed-author:FujiokaShigeruS,
pubmed-author:IshidaHidekiH,
pubmed-author:KishimotoHidehiroH,
pubmed-author:KobayashiSakikoS,
pubmed-author:OhnukiKazunobuK,
pubmed-author:SetoguchiKiyoshiK,
pubmed-author:ShimmuraHiroakiH,
pubmed-author:SuzukiToshihiroT,
pubmed-author:TanabeKazunariK,
pubmed-author:TateYoshikiY,
pubmed-author:TokiDaisukeD
|
| pubmed:copyrightInfo |
Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.
|
| pubmed:issnType |
Electronic
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| pubmed:volume |
23
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
194-203
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| pubmed:meshHeading |
pubmed-meshheading:20624462-Animals,
pubmed-meshheading:20624462-Antibodies, Blocking,
pubmed-meshheading:20624462-Antigens, CD,
pubmed-meshheading:20624462-Bone Marrow Transplantation,
pubmed-meshheading:20624462-CD8-Positive T-Lymphocytes,
pubmed-meshheading:20624462-Cell Proliferation,
pubmed-meshheading:20624462-Chimerism,
pubmed-meshheading:20624462-Humans,
pubmed-meshheading:20624462-Immune Tolerance,
pubmed-meshheading:20624462-Immunologic Memory,
pubmed-meshheading:20624462-Macaca fascicularis,
pubmed-meshheading:20624462-Transplantation Conditioning
|
| pubmed:year |
2010
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| pubmed:articleTitle |
Potential role of host effector memory CD8+ T cells in marrow rejection after mixed chimerism induction in cynomolgus monkeys.
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| pubmed:affiliation |
Department of Urology, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjuku-ku, Tokyo 162-8666, Japan. setoguchi-jua@umin.ac.jp
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|